The present application relates to systems and methods for estimating regional metabolic rate and blood flows of a subject's organ during endovascular interventions.
More particularly, This application describes useful and novel ways to continuously, practically, intra-operatively estimate canonical vascular physiological variables, (Regional Cerebral Blood Flow (rCBF), Regional Cerebral Metabolic Rate (rCMR), Regional Cerebral Vascular Resistance (rCVR), Regional Cerebral Perfused Volume (rCPV)) and; to calculate from these, estimates for recognized (cerebral autoregulation) or new key patho-physiological thresholds (Perfusion Sparing Threshold (PST) (specifically for temperature, Partial Arterial Oxygen Pressure (PaO2), Mean Arterial Pressure (MAP)) and/or new vascular biomarkers, (Reperfusion Severity Index (RSI), Reperfusion Hyperemia Index (RHI)). These values can also be used to determine, and be manipulated for optimal intra-arterial hypothermia and drug delivery. The described application focuses on brain, although the methods described would also work for other organs such as heart and kidneys.
Metabolic rate refers to the rate at which metabolism occurs in living organisms. The metabolic rate of an organ, such as the brain, is generally the rate that the organ uses fuel, oxygen, glucose, etc. Although the brain represents about 2% of total body weight, it consumes between 10-20% of the total oxygen delivered in the resting body. Moreover, unlike other organs, the brain as a whole doesn't have a “resting” state. Rather, the brain is considered to be constantly “active.”
The cerebral rate of oxygen metabolism (CMRO2) of a normal, conscious individual is generally known. The rCBF of a normal, conscious individual is also generally known. Deviations from the norm or from a reference rate may be probative of the relative health of the brain. In this regard, a number of procedures have been proposed to estimate metabolic rates in the brain and/or rCBF using imaging systems, such as positron emission computed tomography (PET), Single Photon Emission Computed Tomography (SPECT), and magnetic resonance imaging (MRI). One such procedure is discussed in U.S. Patent Publication No. 20090198122 entitled “Systems and Methods for Determining Metabolic Rate Using Temperature Sensitive Magnetic Resonance Imaging”, which is incorporated herein by reference. Imaging systems, however, have their drawbacks when it comes to determining metabolic rates and blood flows. Particularly, imaging systems generally only provide a “snapshot” of an organ's metabolic rate at a given time. Repetitive scans are typically not practical or economical, and therefore do not provide an adequate solution. Moreover, these imaging systems cannot be used during endovascular interventions without significantly delaying or interrupting the therapy.
Additionally, almost all drugs are given by oral, intravenous, or dermal routes. Towering experience, expertise, daunting IP, and breathtaking amounts of effort have been marshalled to effectively address the myriad of issues to craft drugs and carriers that can be given in this fashion. Vascular endothelial toxicity is problematic in many drugs, irrespective of how given, and is thought to account for a significant amount of short term and long term morbidity associated with drug treatment. Accordingly, there is a need for systems and corresponding procedures for administering drugs that control their toxicity, ergo their effects on non-target tissue. Additionally correct drug dosing during intra-arterial drug delivery is challenging without knowledge of the regional blood flow, volume of tissue being perfused, and energy metabolism. Accordingly, there is a need for systems and corresponding procedures for using such systems that are not so limited and/or otherwise address one or more of the issues noted above.